Volume 135 · Issue 05 · 2022

这一年（2022年）标志着135^th成立周年中华医学杂志.135年来，该刊见证了中国人民健康状况的巨大变化，见证了现代医学技术在增进健康、减少疾病、延长寿命方面的重要作用，见证了医疗卫生服务和社会保障体系的不断完善。

乙型肝炎病毒（HBV）感染是一个全球性的公共卫生问题，在世界范围内造成高疾病负担。^[1]作为一个肝炎高负担国家，目前我国约有7000万人感染HBV，母婴传播（MTCT）仍然是我国HBV感染的主要方式。^[2]预防母婴传播是消除HBV感染的关键，对HBV感染孕妇及其新生儿进行规范管理可有效切断母婴传播。^[3]新生儿乙肝免疫球蛋白和乙肝疫苗可有效降低HBV阳性孕妇婴儿的新生儿HBV感染。妊娠28周后的围产期抗病毒预防被证明在降低HBV风险方面非常有效（MTCT）。^[4]再者，控制孕妇乙肝感染不仅降低了家庭内传播和母婴垂直传播的风险，^[5]而且还可能降低不良妊娠结局的风险。^[6]因此，了解我国孕妇HBV感染的流行病学特征，更好地规范该人群的预防、诊断、治疗，对于实现世界卫生组织（WHO）提出的“到2030年消除病毒性肝炎这一重大公共卫生威胁”的目标具有重要意义。

强直性脊柱炎（AS）是脊柱关节炎（SpA）的原型，具有脊柱的长期关节炎症。SpA表现还包括银屑病、葡萄膜炎和炎症性肠病，这表明这些疾病可能有一些共同的遗传背景。

空气污染是对人类健康最大的环境威胁之一。2005年，世界卫生组织（WHO）发布了第一个针对颗粒物（PM）、臭氧（O₃）、二氧化氮（否₂)和二氧化硫。^[1]2021年9月22日，世卫组织更新了其AQGs，提供了空气污染对健康不利影响的明确证据，其浓度甚至比以前了解的还要低。^[2]例如，世卫组织AQGs 2021建议PM的年平均浓度_2.5不得过5 μ g/m³而且没有₂不得过10 μ g/m³旺季平均8-h O₃浓度不超过60 μ g/m。^[2,3]作为比较，相应的WHO AQGs 2005值为10 μ g/m³对于PM_2.5和40 μ g/m³对于没有₂，不建议长期使用₃浓度。^[1]

随着社会经济的快速发展、生活水平的提高和生活方式的改变，成人疾病，如心血管疾病、2型糖尿病(T2DM)、高血压、肥胖症等在过去几十年中急剧增加，这在中国人口和个人层面都造成了巨大的经济和健康负担。^[1]成人疾病负担的增加已成为主要的公共卫生问题，近年来我国成人疾病的预防已成为一项艰巨的任务。二零一六年，中国提出了全生命周期健康的概念，并努力将重点从治疗疾病转向预防。鉴于成年期疾病预防效果不佳，建议将成人疾病预防和管理延伸到生命早期，这是生理编程的关键窗口，对全生命周期健康具有深远而持久的影响。^[2,3,4]2018年，《美国医学会杂志》（JAMA）发表的一篇名为《预防心血管疾病，关注妊娠并发症》的文章也说明，怀孕是未来健康的窗口。^[5]

The cancer burden in the United States of America (USA) has decreased gradually. However, China is experiencing a transition in its cancer profiles, with greater incidence of cancers that were previously more common in the USA. This study compared the latest cancer profiles, trends, and determinants between China and USA.

This was a comparative study using open-source data. Cancer cases and deaths in 2022 were calculated using cancer estimates from GLOBOCAN 2020 and population estimates from the United Nations. Trends in cancer incidence and mortality rates in the USA used data from the Surveillance, Epidemiology, and End Results program and National Center for Health Statistics. Chinese data were obtained from cancer registry reports. Data from the Global Burden of Disease 2019 and a decomposition method were used to express cancer deaths as the product of four determinant factors.

In 2022, there will be approximately 4,820,000 and 2,370,000 new cancer cases, and 3,210,000 and 640,000 cancer deaths in China and the USA, respectively. The most common cancers are lung cancer in China and breast cancer in the USA, and lung cancer is the leading cause of cancer death in both. Age-standardized incidence and mortality rates for lung cancer and colorectal cancer in the USA have decreased significantly recently, but rates of liver cancer have increased slightly. Rates of stomach, liver, and esophageal cancer decreased gradually in China, but rates have increased for colorectal cancer in the whole population, prostate cancer in men, and other seven cancer types in women. Increases in adult population size and population aging were major determinants for incremental cancer deaths, and case-fatality rates contributed to reduced cancer deaths in both countries.

The decreasing cancer burden in liver, stomach, and esophagus, and increasing burden in lung, colorectum, breast, and prostate, mean that cancer profiles in China and the USA are converging. Population aging is a growing determinant of incremental cancer burden. Progress in cancer prevention and care in the USA, and measures to actively respond to population aging, may help China to reduce the cancer burden.

Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.

We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. ¹¹C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.

The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.

Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.

Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.

This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high-risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years.

A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group.

In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear.

To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification.

PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = -0.189, P = 0.011 for cg00464519 and r = -0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.

As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.

全膝关节置换术（TKA）后在冠状面上恢复正确的下肢对齐可以减少骨水泥—植入物界面的应力、聚乙烯磨损和植入物松动。负重长腿X线片（LLR）用于评估冠状面的机械轴，识别股骨和胫骨的解剖变异，并在术前计划骨切除程度。然而，下肢的旋转或屈曲可能影响来自LLR的对准参数测量的准确性。此外，已知的旋转相关线性变化可用于将下肢旋转程度与股骨和胫骨的对准参数以及髋-膝-踝(HKA)角度相关联。^[1]

致编辑：慢性气流阻塞(CAO)是慢性阻塞性肺疾病(COPD)的特征，并且由于通常与暴露于有害颗粒或气体相关的气道和/或肺泡异常而发生。^[1]CAO的主要危险因素是吸烟，但接触固体燃料可能会影响CAO的发展。研究发现，固体燃料暴露与CAO的高患病率有关，尤其是在女性中。^[2]比较由固体燃料或烟草烟雾暴露引起的COPD非常重要，因为全球约有30亿人暴露于固体燃料烟雾，10.1亿人吸烟。本研究旨在使用倾向评分匹配（PSM）调查和比较中国西部暴露于固体燃料和烟草烟雾的CAO患者的临床和功能特征。

致编辑：遗传疾病导致生命第一年死亡的35%，并且是重症监护的重要原因。^[1]此前一项基于中国新生儿基因组计划的研究调查了婴儿早期死亡的遗传原因，发现>25%的有基因诊断的死亡新生儿如果及时诊断是可以治愈的。^[2]因此，尽早针对和诊断患有遗传病的新生儿至关重要。根据我们的经验，典型的表型，如特殊的面部特征或多重先天性异常（MCAs），表明遗传病的高风险，并导致医生尽早对新生儿进行基因检测。然而，在实践中，没有典型表型的婴儿在确认遗传诊断之前通常经历漫长且昂贵的诊断过程。此外，美国医学遗传学和基因组学学院（ACMG）和其他国家专业组织最近的一项调查表明，合格的遗传学家不足以满足遗传服务的需求。^[3]ACMG公布了基因检测适应症的一般临床特征。例如，具有强烈暗示遗传原因的表型或家族史数据的患者可以接受基因测试。^[1]然而，研究表明，许多遗传条件的出现再一次或无家族史遗传。^[1]先前的一项研究试图将非表型驱动的小组方法应用于新生儿重症监护室（NICU）的新生儿。^[4]但目前诊断产率仅为3.45%（1/29）。^[4]此外，与基因组筛查相关的经济和伦理问题仍然具有挑战性。因此，基因检测的可用适应症可能会改善遗传病的管理。

致编辑：肝纤维化的特征是肝星状细胞（HSC）的活化和细胞外基质沉积。肝纤维化的发病机制涉及多方面。研究发现，HSC中的内质网应激（ERS）可导致HSC活化，加重肝纤维化。^[1]尽管肝纤维化已被广泛研究，但目前缺乏有效的抗纤维化药物。延胡索乙素(THP)是中草药的有效成分延胡索已有研究发现THP的保肝作用。本研究旨在探讨THP对肝纤维化的影响及其潜在机制。